Endocrine regulation of metabolic crosstalk between liver and brown adipose tissue by natural active ingredients

The escalating global obesity crisis and its associated metabolic disorders have posed a significant threat to public health, increasing the risk of major health issues such as cardiovascular diseases and type 2 diabetes. Central to metabolic regulation are the liver and brown adipose tissue (BAT), which orchestrate glycolipid metabolism, thermogenesis, and energy homeostasis. Emerging evidence highlights the role of natural bioactive compounds-such as polyphenols (e.g., resveratrol, curcumin), alkaloids (e.g., berberine), and terpenoids (e.g., paeoniflorin, shikonin)-in modulating liver-BAT crosstalk. These compounds influence critical pathways, including AMPK activation, PPAR signaling, and UCP1-mediated thermogenesis, to enhance lipid oxidation, suppress gluconeogenesis, and improve insulin sensitivity. This review systematically examines how these natural agents regulate metabolic interplay between the liver and BAT, addressing their effects on energy expenditure, carbohydrate utilization, and lipid mobilization. Key mechanisms involve the suppression of hepatic lipogenesis, promotion of BAT-mediated thermogenesis, and secretion of hepatokines (e.g., FGF21) and batokines that coordinate interorgan communication. By synthesizing preclinical and clinical findings, we highlight the translational potential of dietary interventions and nutraceuticals targeting liver-BAT axis dysfunction. Future research should prioritize mechanistic studies, dose optimization, and personalized approaches to harness these compounds for combating obesity-related diseases. These insights underscore the promise of natural bioactive molecules as adjuvants to lifestyle modifications, offering innovative strategies for metabolic health restoration.